6sge
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Human RHOB-GTP in complex with nanobody B6== | |
| + | <StructureSection load='6sge' size='340' side='right'caption='[[6sge]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6sge]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SGE FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6sge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sge OCA], [https://pdbe.org/6sge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sge RCSB], [https://www.ebi.ac.uk/pdbsum/6sge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sge ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RHOB_HUMAN RHOB_HUMAN] Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells.<ref>PMID:9478917</ref> <ref>PMID:10508588</ref> <ref>PMID:15226397</ref> <ref>PMID:16236794</ref> <ref>PMID:21373644</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The selective downregulation of activated intracellular proteins is a key challenge in cell biology. RHO small GTPases switch between a guanosine diphosphate (GDP)-bound and a guanosine triphosphate (GTP)-bound state that drives downstream signaling. At present, no tool is available to study endogenous RHO-GTPinduced conformational changes in live cells. Here, we established a cell-based screen to selectively degrade RHOB-GTP using F-box-intracellular single-domain antibody fusion. We identified one intracellular antibody (intrabody) that shows selective targeting of endogenous RHOB-GTP mediated by interactions between the CDR3 loop of the domain antibody and the GTP-binding pocket of RHOB. Our results suggest that, while RHOB is highly regulated at the expression level, only the GTP-bound pool, but not its global expression, mediates RHOB functions in genomic instability and in cell invasion. The F-box/intrabody-targeted protein degradation represents a unique approach to knock down the active form of small GTPases or other proteins with multiple cellular activities. | ||
| - | + | A Targeted Protein Degradation Cell-Based Screening for Nanobodies Selective toward the Cellular RHOB GTP-Bound Conformation.,Bery N, Keller L, Soulie M, Gence R, Iscache AL, Cherier J, Cabantous S, Sordet O, Lajoie-Mazenc I, Pedelacq JD, Favre G, Olichon A Cell Chem Biol. 2019 Nov 21;26(11):1544-1558.e6. doi:, 10.1016/j.chembiol.2019.08.009. Epub 2019 Sep 12. PMID:31522999<ref>PMID:31522999</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Cabantous | + | <div class="pdbe-citations 6sge" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: Gence | + | ==See Also== |
| - | [[Category: Lajoie-Mazenc | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| - | [[Category: | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| - | [[Category: | + | *[[Rho GTPase 3D structures|Rho GTPase 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cabantous S]] | ||
| + | [[Category: Favre G]] | ||
| + | [[Category: Gence R]] | ||
| + | [[Category: Lajoie-Mazenc I]] | ||
| + | [[Category: Pedelacq JD]] | ||
| + | [[Category: Soulie S]] | ||
Current revision
Crystal structure of Human RHOB-GTP in complex with nanobody B6
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